The present invention relates to cartridges such as ion exchange cartridges or adsorption cartridges which are useful, for instance, in dialysis. In particular, the present invention relates in general to the regeneration or purification of used dialysate fluids. The present invention further relates to methods of conducting dialysis using certain cartridges and also relates to methods of making the cartridges.
Dialysis is a treatment that removes the waste products and excess fluid that accumulate in the blood as a result of kidney failure. Chronic renal failure is when the renal function has deteriorated to about 25% of normal. This amount of deterioration causes significant changes in the blood chemistry and is about the time that people feel poorly enough that they seek medical care. If medical treatment is sought at that time, progression can be slowed. Late stage chronic renal failure is when kidney function has decreased to 15%. End stage renal failure is when kidney function is at 5% of normal. Death will most likely result without treatment at this point. As of 1998, there were 430,000 patients in the United States diagnosed with chronic renal failure, wherein the average life expectancy of a chronic renal failure patient is 2½ years. Some do live 20 years or more. Also, there are approximately as many patients yearly with acute renal failure as with chronic renal failure, approximately ½ of these patients need treatment. On the whole, acute patients are sicker and less stable than chronic patients. They are frequently in ICU or CCU and can't be moved. Acute patients die, recover kidney function, or go on to become chronic dialysis patients. There is no current cure for renal disease. However, one treatment is transplantation, which is where a human kidney is surgically placed in the body and connected to the bladder. Daily medication is needed to keep the body from rejecting the transplanted kidney. Also, there is peritoneal dialysis (PD). With this treatment, a mild saltwater solution containing dextrose and electrolytes called dialysate is put into the peritoneal cavity. Because there is a rich blood supply to this abdominal cavity, urea and other toxins from the blood and fluid are moved into the dialysate, thereby cleaning the blood. The dialysate is then drained from the peritoneum. Later “fresh” dialysate is again put into the peritoneum.
Also, there is hemodialysis. This is a method of blood purification in which blood is continually removed from the body and passed through a dialyzer (artificial kidney) where metabolic waste and excess water are removed and pH and acid/base balance are normalized. The blood is simultaneously returned to the body. The dialyzer is a small disposable device consisting of a semi-permeable membrane. The membrane allows the wastes, electrolytes, and water to cross but restricts the passage of large molecular weight proteins and blood cells. Blood is pumped across one side of the membrane as dialysate is pumped in the opposite direction across the other side of the membrane. The dialysate is highly purified water with salts and electrolytes added. The machine is a control unit which acts to pump and control pressures, temperatures, and electrolyte concentrations of the blood and the dialysate. The average length of one hemodialysis treatment is 3–5 hours.
There are several types of hemodialysis:
a) Single Pass—hemodialysis is the most common treatment for renal disease. Most hemodialysis treatments are performed with single pass dialysis machines. They are called single pass because the dialysate (cleaning solution) passes by the blood in the dialyzer one time and then is disposed. Single pass dialysis machines generally require:
1) a water source capable of delivering at least 1000–1500 ml/min (assuming a 50% rejection rate by the R.O. system)
2) a water purification system sufficient of providing a continuous flow of 500–800 ml/min of purified water.
3) an electrical circuit of at least 15 amps in order to pump and heal 500–800 ml of water/min.
4) a floor drain or any other receptacle capable of accommodating at least 500 ml of used dialysate/minute as well as the rejected water from the R.O. system.
b) Sorbent Dialysis
1) does not require a continuous water source, a separate water purification machine or a floor drain because it continuously regenerates a small volume of dialysate and incorporates a water treatment system within the machine. Therefore, sorbent systems are truly portable.
2) sorbent systems require only a 5 amp electrical source because they recycle the same small volume of dialysate throughout the dialysis procedure. The heavy duty dialysate pumps and heaters used for large volumes of dialysate in single pass dialysis are not needed.
3) the sorbent system can use 6 liters of tap water from which dialysate is made for an entire treatment.
4) the sorbent system uses a sorbent cartridge—which acts both as a water purifier and as a means to regenerate used dialysate into fresh dialysate. The infusate system acts with it to properly balance the electrolyte composition of the regenerated dialysate.
The sorbent cartridge containing zirconium phosphate (ZrP) and hydrous zirconium oxide (HZO) ion-exchange materials has been historically used for the REDY regeneration hemodialysis system. The scheme of the REDY cartridge is shown in FIG. 1.
The principle of the REDY cartridge is based on the hydrolysis of urea to ammonium carbonate by the enzymatic reaction of urease. The ammonia and ammonium ions are then removed by the zirconium phosphate (NaHZrP) in exchange for the hydrogen ions and Na+ ions, which are counter-ions in the cation exchanger. ZrP also serves as cation exchanger to remove Ca, Mg, K, and all toxic metals in dialysate, thus allowing to maintain a balance of electrolyte level in the patient's blood (Ca, Mg, K) by using an infusate system, as well as providing safety for dialysis treatment with regard to water quality. The carbonate from the urea hydrolysis then combines with the hydrogen ions in NaHZrP to form bicarbonate, which is delivered to the uremic patient as a base to correct for acidosis. The hydrous zirconium oxide (HZO) containing acetate as a counter ion serves as an anion exchanger to remove phosphate from uremic patients for the treatment of hyperphosphatemia. The material also prevents leaching of phosphate from NaHZrP and removes toxic anions (e.g., fluoride) in water that may cause harm to a patient during dialysis. The acetate released during ion exchange is also a base to correct for acidosis by acetate metabolism. The granular activated carbon in the cartridge is responsible for the removal of creatinine, uric acid, and nitrogenous metabolic waste of the patient as well as chlorine and chloramine from water. Thus the REDY regenerative dialysis system is efficient to provide both safety and simplicity of water treatment and hence convenience for hemodialysis. The efficacy and safety record of the system has been well established. Nevertheless, the REDY cartridge can produce a variation of dialysate composition and pH during the treatment with a continuous release of Na+ by the cartridge. Thus the REDY dialysis therapy has to provide several dialysate prescriptions to balance the Na+ level in the patient for the correction of hyper and hyponatremia. Also a conductivity alarm system is generally present to keep the Na+ level in the dialysate below a safe limit with proper dilution. The Na+ and bicarbonate level in the dialysate may vary with the BUN level of the patient.
In the area of peritoneal dialysis (PD), particular emphasis has to be put on (1) a minimum variation of dialysate composition and pH during the PD treatment and (2) cost and size of the cartridge. For example, the adsorption capacity requirement of sorbent PD may be lower than that of REDY cartridge. The variation of dialysate composition is particularly important since PD is a slow treatment with treatment duration up to 2–4 hours per day. Excessive donation of Na+ by the cartridge to the patient should be avoided during the treatment. In order to control the release of Na+, an understanding of the ion exchange mechanism of ZrP with ammonium ions and dialysate cations (Ca, Mg, K, and Na) is needed.
ZrP is an inorganic cation exchange material with the molecular structure as shown below:

It contains both H+ and Na+ as counter-ions, which are responsible for ion exchange. The relative content of these ions in ZrP can be controlled by the pH to which acid ZrP (or H+ZrP) is titrated with NaOH. The composition of the resultant product of titration,
Nax+H2−x+ZrP, may vary during the following ion exchange processes in dialysate:
                                                                        M                +                            ⁢                                                                    Na                    +                                    ⁢                                      H                    +                                    ⁢                  ZrP                                _                            ⁢                            ⁢                              Na                +                                      +                                                                                M                    +                                    ⁢                                      H                    +                                    ⁢                  ZrP                                _                            ⁢                                                          ⁢              K                                =                                                    [                                  Na                  +                                ]                            ⁢                                                [                                                            M                      +                                        ⁢                                          H                      +                                        ⁢                    ZrP                                    ]                                _                                                                    [                                  M                  +                                ]                            ⁢                                                [                                                            Na                      +                                        ⁢                                          H                      +                                        ⁢                    ZrP                                    ]                                _                                                    ⁢                                  ⁢                                                            where                ⁢                                                                  ⁢                                  M                  +                                            =                              NH                4                +                                      ;                          Ca                              2                +                                      ;                          Mg                              2                +                                              ,                      H            +                                              (        i        )                                                                                    M                +                            ⁢                                                                    Na                    +                                    ⁢                                      H                    +                                    ⁢                  ZrP                                _                            ⁢                            ⁢                              H                +                                      +                                                                                M                    +                                    ⁢                                      Na                    +                                    ⁢                  ZrP                                _                            ⁢                                                          ⁢              K                                =                                                    [                                  H                  +                                ]                            ⁢                                                [                                                            M                      +                                        ⁢                                          Na                      +                                        ⁢                    ZrP                                    ]                                _                                                                    [                                  M                  +                                ]                            ⁢                                                [                                                            Na                      +                                        ⁢                                          H                      +                                        ⁢                    ZrP                                    ]                                _                                                    ⁢                                  ⁢                                                            where                ⁢                                                                  ⁢                                  M                  +                                            =                              Na                +                                      ;                          Ca                              2                +                                      ;                          Mg                              2                +                                              ,                      NH            4            +                                              (        ii        )                                                                    Na              2                        ⁢                          CO              3                                +                                                                      Na                  +                                ⁢                                  H                  +                                ⁢                ZrP                            _                        ⁢                        ⁢                                                            Na                  2                  +                                ⁢                ZrP                            _                                +                      NaHCO            3                          ⁢                                  ⁢                                            NaHCO              3                        +                                                                                Na                    +                                    ⁢                                      H                    +                                    ⁢                  ZrP                                _                            ⁢                            ⁢                                                                    Na                    2                    +                                    ⁢                  ZrP                                _                                      +                                          H                2                            ⁢                              CO                3                                              ->                                                    H                2                            ⁢              O                        +                          CO              2                                                          (        iii        )            
The relative release of Na+ and H+ by ZrP during the ion exchange depends on the ion exchange equilibrium of these ions in ZrP with other cations in the liquid phase. The equilibrium may shift as the composition of {overscore (Na+H+ZrP)} and liquid phase continue to change during the ion exchange process.
Based on the ion exchange principle, the Na+ release from ZrP can be controlled by shifting to the conditions that favor the dominant release of H+ ions. This concept can be important for the design of sorbent cartridge formulations for the PD fluid regeneration.
The current method of making ZrP for the REDY cartridge is titrating acid ZrP (H+ZrP) to the pH range 6.25–6.45 in a NaCl/NaAc buffer to produce {overscore (Na+H+ZrP)} with high Na+ content. This will trigger the Na+ release especially in acetate or lactate dialysate with low buffer capacity and at low pH. Thus the ZrP quality made for the REDY cartridge may not be suitable for the PD fluid regeneration application. In order to remove this limitation, as shown in the present invention, a modification is made by using {overscore (Na+H+ZrP)} with lower specified Na+ content. This material can be made by titrating the acid ZrP (H+ZrP) to a lower pH range 5.5–6.0 in deionized water. Another limitation of the REDY cartridge for PD treatment is that the hydrous zirconium oxide loaded with acetate is an acidic material. Thus the low pH of dialysate resulted from the acidity of this material will trigger a release of Na+ and an initial loss of bicarbonate due to the reaction.

If the current REDY cartridge is used for PD treatment, it may produce a continuous rise of Na+ concentration up to 170 mEq/l due to dominant Na+ exchange throughout the treatment. In addition, an initial dip of Na+. HCO3 and pH may occur due to short time H+ exchange.
Accordingly, in the area of dialysis, especially with respect to PD treatment, it would be beneficial to overcome one or more of the above-described disadvantages.